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Low-molecular-weight protein (LMP)2LMP7 abnormality underlies the downregulation of human leukocyte antigen class I antigen in a hepatocellular carcinoma cell line
Background: Tumor cells may alter the expression of numerous components involved in antigen-processing machinery to decrease human leukocyte antigen (HLA) class I expression, allowing the tumor cells to escape immune surveillance. The purpose of the present study was to investigate the involvement o...
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Published in: | Journal of gastroenterology and hepatology 2007-07, Vol.22 (7), p.1155-1161 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | Background: Tumor cells may alter the expression of numerous components involved in antigen-processing machinery to decrease human leukocyte antigen (HLA) class I expression, allowing the tumor cells to escape immune surveillance. The purpose of the present study was to investigate the involvement of these components in the downregulation of HLA class I expression in human hepatocellular carcinoma cell line BEL7404. Methods: Expression of HLA-I and antigen presentation-related genes were analyzed by flow cytometry and polymerase chain reaction. The HLA class I-deficient BEL7404 cell was transfected with the low-molecular-weight protein (LMP) 2 and LMP7 gene and were analyzed by flow cytometry for restoration of surface HLA class I expression. Results: The BEL7404 cells downregulated the expression of HLA class I antigen and lacked expression of LMP2 and LMP7. Interferon (IFN)- gamma treatment increased the expression of LMP2 but not LMP7. The LMP2-transfected BEL7404 cells or LMP2 and LMP7-cotransfected cells restored surface HLA class I expression while LMP7-transfected cells did not. However, in IFN- gamma -treated BEL7404 cells, transfection with the LMP7 gene induced more HLA class I expression than mock transfection. Conclusions: The LMP2 gene was required for the expression of HLA class I molecules in BEL7404. The LMP7 was not the major reason for loss of HLA class I in BEL7404 cells, although the supply of exogenous LMP7 could increase surface expression of HLA class I antigen. |
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ISSN: | 0815-9319 1440-1746 |
DOI: | 10.1111/j.1440-1746.2006.04421.x |